This invention relates to biomaterials of enhanced biocompatibility, in particular to a polypropylene biomaterial.
Polypropylene serves important medical and bioanalytical uses as a filtration membrane, as a gas permeable, liquid impermeable membrane in blood oxygenators, as a container for blood samples, and so forth. To improve compatibility with blood, heparin is conventionally used as an anticoagulant. However, medical and bio-analytical applications could alternatively be enhanced by improving biocompatibility of polypropylene biomaterial.
As indicated, an important use of polypropylene is as a hollow fiber membrane in blood oxygenators. Typically, blood flows externally to the hollow fiber membrane and may contact the oxygenator housing, which is commonly polycarbonate. Therefore, it would also be beneficial to improve the biocompatibility of polycarbonate biomaterial.
As illustrated by Campbell and Lyman, Journal of Polymer Science, 55: 169 (1961), it is known to form a chlorinated polyhydrocarbon using a chlorinating agent and white light catalysis either in a liquid reaction medium or in a gas reaction. Particularly described is chlorination of polypropylene and of poly(4-methyl-1-pentene) in a chlorinated solvent. Also described is chlorination of poly(4-methyl-1-pentene) in an aqueous suspension in which skeins of yarn of the polymer were chlorinated, and in a gas reaction in which the polymer powder was shaken in an atmosphere of chlorine gas. Surface chlorination was observed for skeins of fiber.
Also known as exemplified by Markovich et al, Anal. Chem. 63: 185 (1991) is the use of spacer arm chemical species such as aminopropylsilanes for covalently bonding biocompatibility-enhancing phospholipids to a silica surface, so as to provide the silica with an immobilized artificial membrane surface. The spacer armproviding molecule combines with the length of the covalently bonded acyl chain of the phospholipid to provide a sterically beneficial spacing of the phospholipid from the silica surface.
Covalent bonding of biocompatibility-enhancing compounds to polymeric substrates including polypropylene to provide biocompatible solid surfaces, is described in U.S. Pat. No. 4,973,493 to Guire. The method uses a chemical linking moiety having a reactive group for covalently bonding to the compounds, and having a photochemically reactive group for covalently binding to the polymeric substrate. The photochemical reaction is effected after the chemical linking moiety is attached to a biocompatibility-enhancing compound. As a consequence, a large steric bulk is attached to the polymeric substrate.
Problems with immobilized artificial coatings have included an insufficiently dense coverage of the biomaterial surface and non-uniformity of coverage with substantial gaps. As a result, body fluid constituents may interact with uncoated regions and with each other, with negative impact on biocompatibility.
Therefore, there remains a need for a process for enhancing biomaterial biocompatibility, and in particular for making biomaterials having improved density and uniformity of a biocompatibility-providing coating. Importantly, the artificially coated biomaterial would continue to possess beneficial physical properties of the biomaterial.